The renin-angiotensin system (RAS) and kallikrein-kinin system (KKS) may control renal salt and water excretion by acting intrarenally. Preliminary data show that, in vitro, angiotensin II (AII) directly alters proximal tubule Na transport, and that lysyl-bradykinin (LBK) inhibits ADH action in the cortical collecting tubule (CCT). This proposal will further address these questions: 1) Does AII specifically stimulate NaCl transport? If so, is this effect on electroneutral, electrogenic, or passive NaCl transport? What is the role of calcium in AII's action? 2) Does AII alter ion and water transport in the CCT, and, if so, are calcium cAMP or prostaglandins involved? 3) Does LBK effect Na, K, Cl, or HCO3 transport in the CCT? If so, are prostaglandins involved? 4) Which cell type in the CCT responds to LBK? These studies have significant potential clinical relevance. The normal natriuresis and diuresis seen with elevated perfusion pressure ("pressure natriuresis") is abnormal in some patients with essential hypertension. The RAS and KKS are probably important in the normal response, and may play a role in the abnormal one. The applicant is committed to developing a productive career in academic medicine and membrane transport research. The present environment is ideal for such growth. The Department of Medicine and the Renal Division actively and carefully foster growth of new faculty. Most importantly, the applicant's laboratory is located within a multidisciplinary group of established epithelial transport investigators. The cross-fertilization of ideas and the standards of scientific excellence present in this environment should permit the applicant to rapidly achieve independence.